The systemic use of steroids and habitual alcohol
intake are two major causative factors in the development of idiopathic
osteonecrosis of the femoral head (ONFH). To examine any interaction
between oral corticosteroid use and alcohol intake on the risk of
ONFH, we conducted a hospital-based case-control study of 71 cases
with ONFH (mean age 45 years (20 to 79)) and 227 matched controls
(mean age 47 years (18 to 79)). Alcohol intake was positively associated
with ONFH among all subjects: the adjusted odds ratio (OR) of subjects
with ≥ 3032 drink-years was 3.93 (95% confidence interval (CI) 1.18
to 13.1) compared with never-drinkers. When stratified by steroid use,
the OR of such drinkers was 11.1 (95% CI 1.30 to 95.5) among those
who had never used steroids, but 1.10 (95% CI 0.21 to 4.79) among
those who had. When we assessed any interaction based on a two-by-two
table of alcohol and steroid use, the OR of those non-drinkers who
did use steroids was markedly elevated (OR 31.5) compared with users
of neither. However, no further increase in OR was noted for the
effect of using both (OR 31.6). We detected neither a multiplicative
nor an additive interaction (p for multiplicative interaction 0.19;
synergy index 0.95), suggesting that the added effect of alcohol
may be trivial compared with the overwhelming effect of steroids
in the development of ONFH. Cite this article:
An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-β enhances the reexpression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco’s modified eagles medium)/ITS+Premix/TGF-β1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically. Pellets cultured in DMEM/ITS+/TGF-β1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-β1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-β is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes.
An international faculty of orthopaedic surgeons
presented their work on the current challenges in hip surgery at
the London Hip Meeting which was attended by over
400 delegates. The topics covered included femoroacetabular impingement, thromboembolic
phenomena associated with hip surgery, bearing surfaces (including metal-on-metal
articulations), outcomes of hip replacement surgery and revision
hip replacement. We present a concise report of the current opinions
on hip surgery from this meeting with appropriate references to
the current literature.
The World Health Organization (WHO) launched
the first Global Patient Safety Challenge in 2005 and introduced
the ‘5 moments of hand hygiene’ in 2009 in an attempt to reduce
the burden of health care associated infections. Many NHS trusts
in England adopted this model of hand hygiene, which prompts health
care workers to clean their hands at five distinct stages of caring
for the patient. Our review analyses the scientific foundation for
the five moments of hand hygiene and explores the evidence, as referenced
by WHO, to support these recommendations. We found no strong scientific
support for this regime of hand hygiene as a means of reducing health
care associated infections. Consensus-based guidelines based on
weak scientific foundations should be assessed carefully to prevent
shifting the clinical focus from more important issues and to direct
limited resources more effectively. We recommend caution in the universal adoption of the WHO ‘5
moments of hand hygiene’ by orthopaedic surgeons and other health
care workers and emphasise the need for evidence-based principles
when adopting hospital guidelines aimed at promoting excellence
in clinical practice.
The identification of the extent of neural damage
in patients with acute or chronic spinal cord injury is imperative for
the accurate prediction of neurological recovery. The changes in
signal intensity shown on routine MRI sequences are of limited value
for predicting functional outcome. Diffusion tensor imaging (DTI)
is a novel radiological imaging technique which has the potential
to identify intact nerve fibre tracts, and has been used to image
the brain for a variety of conditions. DTI imaging of the spinal
cord is currently only a research tool, but preliminary studies
have shown that it holds considerable promise in predicting the
severity of spinal cord injury. This paper briefly reviews our current knowledge of this technique.
The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA. The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105). MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475). The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.
We describe a 63-year-old man who had xanthomatosis of the right tendo Achillis. He had undergone excision of the left tendo Achillis 17 years earlier without reconstruction for the same condition. The neurological history and examination were normal. Blood investigations showed hypercholestrolaemia, for which he was being treated with statins. He was referred with pain in the right tendo Achillis and problems with footwear. He was treated by excision of the right tendo Achillis, the xanthomatous nodules and the involved skin, followed by reconstruction with a cadaver bone-tendon graft. At follow-up eight months postoperatively, the scar had healed well. He walked without pain and could wear any type of shoe. Plain radiographs showed that the bone graft had healed. The American Orthopaedic Foot and Ankle Society hindfoot score was 95/100. The patient’s subjective evaluation of the result was very good.
In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients. We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.
We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45°C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia. The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung.
We report a case of osteonecrosis of the femoral head in a young man who is a carrier of the prothrombin gene mutation. We suggest that an electrical injury to his lower limb may have triggered intravascular thrombosis as a result of this mutation with subsequent osteonecrosis of the femoral head. No case of osteonecrosis of the femoral head secondary to a distant electrical injury has previously been reported.
Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.
Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. Trauma patients are at risk of progressive organ dysfunction from what appears to be an uncontrolled immune response. The availability of improved techniques of molecular diagnosis has allowed investigation of the role of genetic variations in the inflammatory response to post-traumatic complications and particularly to sepsis. This review examines the current evidence for the genetic predisposition to adverse outcome after trauma. While there is evidence supporting the involvement of different polymorphic variants of genes in determining the post-traumatic course and the development of complications, larger-scale studies are needed to improve the understanding of how genetic variability influences the responses to post-traumatic complications and pharmacotherapy.
Polymethylmethacrylate remains one of the most enduring materials in orthopaedic surgery. It has a central role in the success of total joint replacement and is also used in newer techniques such as percutaneous vertebroplasty and kyphoplasty. This article describes the current uses and limitations of polymethylmethacrylate in orthopaedic surgery. It focuses on its mechanical and chemical properties and links these to its clinical performance. The behaviour of antibiotic-loaded bone cement are discussed, together with areas of research that are now shedding light upon the behaviour of this unique biomaterial.
Avascular necrosis of the femoral head creates considerable morbidity in successful renal transplant recipients who are generally young and expect active lifestyles. Total hip replacement is considered the treatment of choice in these patients, but surgeons may be wary because of a supposed increase in the risk of infection and other complications. A review of the literature reveals that cemented hip arthroplasty provides good to excellent functional outcomes for renal transplant patients. Most authors have found that the risk of infection is not increased despite chronic immunosuppression, but the rates of general complications are and should be anticipated and treated. There is a high rate of early failure in these patients because of their young age and diffuse osteopenia as a result of secondary hyperparathyroidism related to the underlying renal disease and chronic steroid use. Recent studies have found that despite decreased bone stock in these patients, porous-coated prostheses are not contraindicated.
The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats. Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month. The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.
Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal ( Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.
We evaluated the concentrations of chromium and cobalt ions in blood after metal-on-metal surface replacement arthroplasty using a wrought-forged, high carbon content chromium-cobalt alloy implant in 64 patients. At one year, mean whole blood ion levels were 1.61 μg/L (0.4 to 5.5) for chromium and 0.67 μg/L (0.23 to 2.09) for cobalt. The pre-operative ion levels, component size, female gender and the inclination of the acetabular component were inversely proportional to the values of chromium and/or cobalt ions at one year postoperatively. Other factors, such as age and level of activity, did not correlate with the levels of metal ions. We found that the levels of the ions in the serum were 1.39 and 1.37 times higher for chromium and cobalt respectively than those in the whole blood. The levels of metal ions obtained may be specific to the hip resurfacing implant and reflect its manufacturing process.
